Usually, proteins are each folded to form the specific native structure thereof, thereby exerting biological functions. When the proteins are misfolded, however, they may aggregate to form β-sheet-rich fibers (i.e., to form amyloid). Aggregates (e.g., oligomers, proto-fibrils, fibers) produced through this amyloid formation are known to cause various dysfunctions (these disorders are generally referred to as “amyloid diseases”). Here, 20 or more proteins have been identified as substances responsible for the amyloid diseases. Example of such amyloid known include: amyloid β, tau protein in Alzheimer's disease; α-synuclein in Parkinson's disease; amylin in diabetes mellitus; transthyretin in systemic amyloidosis; and huntingtin in Huntington's disease.
For example, as for amyloid β (abbreviated to Aβ), which is a causative amyloid of Alzheimer's disease, inhibitors of enzymes mediating the production of Aβ from a precursor protein, promoters of Aβ-degrading enzymes, immunotherapy, Aβ aggregation inhibitors, and the like are known as strategies to develop therapeutic drugs targeting these pathogenic amyloids.
On the other hand, it has been reported as to Aβ that a Met-oxidized form of an Aβ peptide (the sulfur atom of the Met residue is oxidized to sulfoxide (—S═O—)) remains in a small amount in vivo, and the Met-oxidized form is less aggregable as compared with the native Aβ peptide (Non Patent Literatures 1 to 3). From these viewpoints, the present inventors reported that oxidized forms of Aβ peptides are obtained by the oxidation of the Aβ peptides using a flavin photocatalyst having an Aβ-binding site represented by the formula (a), and these oxidized forms of Aβ peptides suppress the aggregation of Aβ (Non Patent Literature 4).
